The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

Abstract

Chronic myeloid leukaemia (CML) is a hematopoietic neoplasm defined by the chromosome translocation t(9;22) and the related oncogene, BCR‐ABL1. In most patients, leukaemic cells can be kept under control using BCR‐ABL1‐targeting drugs. However, many patients relapse which remains a clinical challenge. In particular, patients with advanced (accelerated or blast phase) CML have a poor prognosis. So far, little is known about molecular and cellular interactions and features that contribute to disease progression and drug resistance in CML. One key prognostic factor at diagnosis is marked basophilia. However, although basophils are well‐known multifunctional effector cells, their impact in CML remains uncertain. In this article, we discuss the potential role of basophils as active contributors to disease evolution and progression in CML. In particular, basophils serve as a unique source of inflammatory, angiogenic and fibrogenic molecules, such as vascular endothelial growth factor or hepatocyte growth factor. In addition, basophils provide vasoactive substances, like histamine as well as the cytokine‐degrading enzyme dipeptidyl‐peptidase IV which may promote stem cell mobilization and the extramedullary spread of stem and progenitor cells. Finally, basophils may produce autocrine growth factors for myeloid cells. Understanding the role of basophils in CML evolution and progression may support the development of more effective treatment concepts.

How I investigate basophilia in daily practice

“…CD203c is the most specific marker to identify basophil and permit a reliable quantification in PB and BM. 23 A study by Zehwan et al stated that the combined positivity of CCR3 (CD193) and CD123…”

“…22 Other markers commonly used in the FCM panel can help to identify normal basophils; some of them are available in the majority of clinical laboratory (CD22+ CD9+ CD36+ CD25+dim CD19-CD15-CD64-) and others are not commonly analysed (IgE+ CD88+ FcεRI+ CDw17+). 23 Abnormal immunophenotype is a common finding for neoplastic basophils. Under-expression of CD38 is recurrent among CML patients; some cases may also show aberrant expression of CD64, HLA-DR, and CD123.…”

“…38 The percentage of basophils in the PB and in the BM is an independent prognostic factor. 23,[39][40][41] A study by Kantarjian et al stated that patients with a higher percentage of circulating basophils have lower survival outcomes. 37 Many authors suggest that an increased number of basophils in PB might be an indicator of disease severity.…”

“…37 Many authors suggest that an increased number of basophils in PB might be an indicator of disease severity. 23,[40][41][42][43] It lead the World Health Organization (WHO) 44…”

Association between Hasford Scoring System and Hematologic Response in Chronic and Accelerated Phase of Chronic Myelocytic Leukemia Patient with Imatinib for Three Months

“…Basophil also produced autocrine growth factor in CML. 6 Thomas also stated that Sokal score was no longer the best suited to predict CML patients survival. 7 Dybko stated that Hasford score was still usefull as a tool to differentiate low and intermediate risks in achieving molecular response where as Sokal and EUTOS did not.…”